Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To estimate the prevalence of chronic granulomatous disease (CGD) in Sweden, an inquiry asking for known and possible CGD cases was mailed to paediatric, internal medicine and infectious disease departments all over Sweden. The detected patients were characterized as to genetics and the clinical presentation. Twenty-one patients (belonging to 16 different families) were found, corresponding to a prevalence of approximately 1/450,000 individuals. The patients with X-linked disease, lacking a functional gp91phox protein (n = 12), comprised 57% and 43% of the patients had an autosomal recessive (AR) disease lacking p47phox (n = 7) or p67phox (n = 1), respectively. All unrelated patients with X-linked disease displayed different gene abnormalities such as point mutations predicting nonsense (n = 3), missense (n = 1) or splice site mutations (n = 2), but also a total deletion and a unique 40 base pair duplicature insertion. The patients with p47phox-deficiency showed a GT deletion at a GTGT tandem repeat, and the p67phox-deficient patient displayed a heterozygous in-frame deletion of AAG combined with a large deletion in the other allele. Three patients died during the study period, two from pseudomonas cepacia infections. Patients with X-linked disease had more frequent infections (mean of 1.7 per year), than the patients with AR inheritance (0.5 infections per year). The most common infections were dermal abscesses (n = 111), followed by lymphadenitis (n = 82) and pneumonias (n = 73). Inflammatory bowel disease-like symptoms, mimicking Crohn's disease of the colon, was seen in three CGD patients.
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PMID:Prevalence, genetics and clinical presentation of chronic granulomatous disease in Sweden. 864 57

New sources of human and mouse mast cells, which were isolated from individual organs (i.e., lung, colon, synovium, skin, uterus, heart), developed from progenitors in vitro in the presence of stem cell factor and/or interleukin (IL)-3, or enriched from fetal or adult blood, spleen or bone marrow by cell sorting, have made possible new studies of the cell biology of mast cells. Advances resulting from these new mast cell sources as well as from new methods for labeling specific products in subcellular sites and structures in resting and functional mast cells are the subject of this review. Specific advances discussed are as follows: identification of an Fc epsilonRI+ c-kit- mouse basophil population from bone marrow and spleen that is associated with IL-4 production and an Fc epsilonRI- c-kit- granulated mouse mast cell progenitor in fetal blood; identification of hyperplasia and functional activation of human skin mast cells in vivo when exposed to recombinant stem cell factor and spontaneous degranulation in X-linked immunodeficient mouse mast cells; use of an enzyme-affinity-gold method to detect histamine in mature and immature human mast cell granules, in secretion and recovery of histamine during anaphylactic degranulation of human lung mast cells ex vivo, and in secretion of histamine in vivo by piecemeal degranulation of IL-4 transgenic mouse mast cells in inflammatory eye disease and of human gut mast cells in inflammatory bowel disease; use of immunogold methods to localize cyclooxygenase and tumor necrosis factor-alpha to subcellular structures in human and rat mast cells and to localize the Charcot-Leyden crystal protein in human basophils to aid in the identification of mast cells arising in mixed cellular populations; use of a low-density lipoprotein (LDL)-gold affinity method to demonstrate a rat mast cell granule-mediated uptake of LDL by macrophages in peritoneal fluid.
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PMID:New aspects of mast cell biology. 930 24

Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. We report the first major genomewide screen of multiplex families with RA gathered in the United States. The North American Rheumatoid Arthritis Consortium, using well-defined clinical criteria, has collected 257 families containing 301 affected sibling pairs with RA. A genome screen for allele sharing was performed, using 379 microsatellite markers. A nonparametric analysis using SIBPAL confirmed linkage of the HLA locus to RA (P < .00005), with lambdaHLA = 1.79. However, the analysis also revealed a number of non-HLA loci on chromosomes 1 (D1S235), 4 (D4S1647), 12 (D12S373), 16 (D16S403), and 17 (D17S1301), with evidence for linkage at a significance level of P<.005. Analysis of X-linked markers using the MLOD method from ASPEX also suggests linkage to the telomeric marker DXS6807. Stratifying the families into white or seropositive subgroups revealed some additional markers that showed improvement in significance over the full data set. Several of the regions that showed evidence for nominal significance (P < .05) in our data set had previously been implicated in RA (D16S516 and D17S1301) or in other diseases of an autoimmune nature, including systemic lupus erythematosus (D1S235), inflammatory bowel disease (D4S1647, D5S1462, and D16S516), multiple sclerosis (D12S1052), and ankylosing spondylitis (D16S516). Therefore, genes in the HLA complex play a major role in RA susceptibility, but several other regions also contribute significantly to overall genetic risk.
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PMID:A genomewide screen in multiplex rheumatoid arthritis families suggests genetic overlap with other autoimmune diseases. 1125 50

A 30-year-old man with underlying Wiskott-Aldrich syndrome, which is a rare X-linked congenital immunodeficiency syndrome characterized by recurrent infections, thrombopenia, eczema and hematopoietic malignancies, presented with bloody diarrhea. Endoscopic and histological evaluation was compatible with ulcerative colitis. Congenital immune defects are paralleled by enterocolitis mimicking inflammatory bowel disease in a substantial number of patients. Despite therapy with prednisolone and 5-ASA compounds, the patient described here experienced a relapse of the colitis twice. Subsequently a JC virus infection of the central nervous system was diagnosed, and he died due to progressive multifocal leukencephalopathy.
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PMID:Ulcerative colitis in a patient with Wiskott-Aldrich syndrome. 1224 10

We describe 2 cases of autosomal recessive chronic granulomatous disease (CGD) in 2 sisters presenting with a picture consistent with inflammatory bowel disease. The index case is a 10-year-old girl with a history of refractory Crohn's colitis treated with aggressive immunosuppressive therapy whose course subsequently was complicated by central nervous system aspergillosis. Additional evaluation showed a diagnosis of CGD, an underlying immunodeficiency in which phagocytes fail to produce microbicidal reactive oxygen intermediates because of inherited defects in the reduced form of nicotinamide-adenine phosphate dinucleotide (NADPH) oxidase. The diagnosis of a typically X-linked inherited disease in our female patient suggested that she had 1 of the 3 less common autosomal recessive forms of the disease. This was confirmed by studies showing the absence of the p47(phox) subunit of NADPH oxidase in her neutrophils and the presence of a homozygous dinucleotide deletion in the neutrophil cytosolic factor 1 gene that encodes p47(phox). Additional analyses of members of the patient's immediate family showed the same homozygous mutation in 2 siblings, 1 of whom also developed chronic colitis consistent with a diagnosis of Crohn's disease. These 2 cases emphasize the importance of high clinical suspicion for an alternative diagnosis of immune deficiency in the setting of presumed inflammatory bowel disease and opportunistic infection.
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PMID:Chronic granulomatous disease caused by a deficiency in p47(phox) mimicking Crohn's disease. 1529 Jun 62

Enteroendocrine cell dysgenesis was observed in 3 patients with intestinal failure of unknown cause. Enteroendocrine cell dysgenesis is a congenitally acquired life-threatening malabsorptive condition with a unique clinical phenotype paired with a histologically identifiable disease pattern. Two cases were first presented at the Ninth International Small Bowel Transplantation Symposium, Brussels 2005, and were subsequently published (N Engl J Med 2006;355:270). We now present the histopathologic and immunohistochemical findings of the gastric antrum, small bowel, and colon in greater detail. The clinical phenotype of the patients was unusual in that the affected patients demonstrated profound malabsorption of all nutrients, except water, from birth. The small intestine in each patient demonstrated almost no abnormality, except a near absence of endocrine cells in the mucosa. The colon appeared similarly affected. Known causes of congenital malabsorption, inflammatory, and infectious causes of diarrhea were excluded. The defect is secondary to point mutations in NEUROG3, which result in an arrest of endocrine cell development in the small intestine and colon. This work describes the pathologic characterization of enteroendocrine cell dysgenesis using routine techniques. The pattern of injury is distinct from other histopathologically assessed congenital malabsorptive conditions such as microvillus inclusion disease, tufting enteropathy, and abetalipoproteinemia. It is also easily distinguished from inflammatory conditions such as food allergy, gluten-sensitive enteropathy, autoimmune enteropathy, IPEX (immune dysfunction, polyendocrinopathy, enteropathy, and X-linked inheritance), and inflammatory bowel disease. The histopathology of disease is similar to what has been found transiently in a single patient with autoimmune polyglandular syndrome type I.
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PMID:Enteroendocrine cell dysgenesis and malabsorption, a histopathologic and immunohistochemical characterization. 1725 90

Chronic granulomatous disease (CGD) was first described in the 1950s and has become a paradigm for genetic neutrophil diseases. It is characterized by recurrent infections with a narrow spectrum of bacteria and fungi as well as a common set of inflammatory complications most notably including inflammatory bowel disease. Over the last half century major advances in management have profoundly altered the major clinical issues and the life expectancy of CGD. With X-linked and autosomal recessive forms, it has been an important disease for the development of bone marrow transplantation and gene therapy. Some of the recent developments in infectious syndromes, inflammatory complications, and curative approaches are discussed in this review.
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PMID:Chronic granulomatous disease. 1950 59

Inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn's disease are chronic and relapsing conditions, characterized by abdominal pain, diarrhea, bleeding and malabsorption. IBD has been considered a hyperinflammatory state due to disturbed interactions between the immune system and the commensal bacterial flora of the gut. However, there is evidence that Crohn's disease might be the consequence of a reduced release of pro-inflammatory cytokines and an impaired acute inflammatory response, thereby suggesting that IBD might be an immunodeficiency rather than an excessive inflammatory reaction. This theory has been supported by observations in patients with primary immunodeficiencies such as the Wiskott-Aldrich syndrome and IPEX (immunodysregulation, polyendocrinopathy, enteropathy, X-linked syndrome). In contrary, defects in the anti-inflammatory down-regulation of the immune response as they are seen in patients with Mendelian defects in the IL10 signaling pathway support the hyper-inflammatory theory. In this review, we describe and discuss primary immunodeficiencies associated with IBD and show that the bowel is a highly sensitive indicator of dysregulations, making IBD a model disease to study and identify key regulators required to balance the human mucosal immune system.
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PMID:Inflammatory bowel disease: is it a primary immunodeficiency? 2199 82

Chronic granulomatous disease (CGD), a genetically heterogeneous primary X-linked or autosomal recessive immunodeficiency, can manifest with gastrointestinal symptoms, including colitis or Crohn's disease. The frequency of CGD carriers among those with chronic colitis/inflammatory bowel disease is unknown. We underwent a pilot study examining the value of prospectively screening patients with chronic colitis/inflammatory bowel disease (IBD) for either CGD or the carrier state of CGD. No carriers of CGD or patients with CGD were detected among 120 patients. Three patients had inconclusive results and the assay was normal on repeat testing. We conclude that routine screening for CGD was not instructive in this cohort of chronic colitis or IBD patients.
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PMID:Utility of screening for chronic granulomatous disease in patients with inflammatory bowel disease. 2208 1

Wiskott-Aldrich Syndrome (WAS) is a severe X-linked Primary Immunodeficiency that affects 1-10 out of 1 million male individuals. WAS is caused by mutations in the WAS Protein (WASP) expressing gene that leads to the absent or reduced expression of the protein. WASP is a cytoplasmic protein that regulates the formation of actin filaments in hematopoietic cells. WASP deficiency causes many immune cell defects both in humans and in the WAS murine model, the Was(-/-) mouse. Both cellular and humoral immune defects in WAS patients contribute to the onset of severe clinical manifestations, in particular microthrombocytopenia, eczema, recurrent infections, and a high susceptibility to develop autoimmunity and malignancies. Autoimmune diseases affect from 22 to 72% of WAS patients and the most common manifestation is autoimmune hemolytic anemia, followed by vasculitis, arthritis, neutropenia, inflammatory bowel disease, and IgA nephropathy. Many groups have widely explored immune cell functionality in WAS partially explaining how cellular defects may lead to pathology. However, the mechanisms underlying the occurrence of autoimmune manifestations have not been clearly described yet. In the present review, we report the most recent progresses in the study of immune cell function in WAS that have started to unveil the mechanisms contributing to autoimmune complications in WAS patients.
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PMID:Autoimmunity in wiskott-Aldrich syndrome: an unsolved enigma. 2282 11


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